The use of so-called ophthalmological viscoelastic devices (OVDs) in ophthalmological interventions for the protection of tissues and implants and for the reduction of mechanical forces, which can lead to damage during the preparation and execution of an operative or diagnostic intervention, has been known for many years. These OVDs are as a rule aqueous polymer solutions that are adapted to the conditions of the human eye by adjustment of a specific pH value and a specific osmolarity (adjustment of the polymer-dependent, colloid-osmotic pressure as well as the osmotic pressure that is determined by the contained inorganic salts). In particular, hyaluronic acid and its physiologically compatible salts, chondroitin sulfate, and hydroxypropyl methylcellulose are known as base polymers for these preparations.
A frequent use of these substances is to be found in the fact that in a cataract operation—that is when replacing the natural eye lens—the eye chamber and the capsular bag between the removal of the natural lens and the implantation of the artificial new lens are filled with the viscoelastic device, so as to avoid a collapse of this cavity. At the same time, the viscoelastic devices protect the affected tissues and support the sliding capacity of the instruments and implants used. In the further course of the operation, the viscoelastic devices must then be removed.
As a result of this circumstance, it is necessary that opthalmological viscoelastic devices have the following flow properties: in the absence of shear forces, dimensionally stable gels must form; otherwise, it must be possible to readily inject and aspirate them through a syringe needle. An appropriate flow property is very well approximated by solutions of hyaluronic acid and its salts. Hyaluronic acid is a naturally occurring biopolymer from the group of glucose aminoglucans. Although the substance is widely dispersed, it is nevertheless cost-intensive to tap productive sources for high molecular weight hyaluronic acid. For the most part, this is done by two methods—namely, the extraction from animal tissues or by a fermentation production. The products from animal sources surpass the fermentation-produced products as a rule in the characteristics dependent on the molecular weight. Thus, starting products of commercially available products with particularly high zero-shear viscosities are mostly of animal origin and exhibit an average molecular weight of 4 million daltons. The fermentation-produced products have a molecular weight of approximately 2.5 million daltons and correspondingly low zero-shear viscosities. The use of products of animal origin is connected with the risk of a BSE/TSE transmission. Furthermore, their use as well as the use of fermentation-produced products requires a strict control of the endotoxin content, since endotoxins can contaminate the product during production.
Hyaluronic salt solutions are not only used in ophthalmology, but rather also in rheumatology and orthopedics—for example, arthrosis treatment. On the one hand, by replenishing the synovial fluid, the sliding capacity of the cartilage and the absorption of abruptly acting forces can be improved; on the other hand, inflammation-inhibiting effects are discussed. Also, uses in dermatology and plastic surgery, for example, for injection under wrinkles, have found large proliferation.
Although hyaluronic acid salt solutions exhibit good technical properties and aside from the aforementioned uses, have captured additional usage areas in medicine, there is nevertheless a need to obtain corresponding products from simpler, more easily accessible and less cost-intensive sources. Thus, in the international application, WO2008/035372, Reliance Life Sciences Pvt. Ltd., the proposal is made to obtain hyaluronic acid from bacteria. These fermentation-obtained products, however, have limited rheological properties due to their lower molecular weight, in comparison with hyaluronates from higher organisms. Furthermore, the bacterially produced hyaluronic acid is subject to the main disadvantage of this class of substances, which consists in that the aqueous solutions are thermally sensitive and therefore must be cooled during storage and transport. Furthermore, the preparations specimens lose considerably in viscosity in a steam sterilization due to a reduction of the molecular weight. It is particularly the viscosity in solution, however, which is the decisive technical characteristic of the products, so that an obvious disadvantage is present here.
Thus, there has not been a lack of attempts to use synthetic polysaccharide ethers, such as hydroxypropyl methylcellulose, for this use. Thus, U.S. Pat. No. 5,422,376, Dow Chemical, proposes the synthesis of a viscoelastic material based on a hydroxypropyl methylcellulose with a molecular weight between 375,000 and 420,000 daltons. Hydroxypropyl methylcellulose (HPMC) has proved to be excellent with respect to body tolerance and can be easily obtained from cellulose raw materials, as they extensively exist in nature. The disadvantage, however, is that the viscosity of aqueous preparations is not dependent on shear force in the manner in which this is known from hyaluronic acid. Stable HPMC solutions can therefore not be metered simply through a syringe needle. Furthermore, to attain high zero-shear viscosities, such high concentrations would be required that compatible osmolalities could not be maintained.